Nissen C, Tichelli A, Gratwohl A, Speck B, Milne A, Gordon-Smith E C, Schaedelin J
Preclinical and Clinical Research, Sandoz, Ltd, Basel, Switzerland.
Blood. 1988 Dec;72(6):2045-7.
Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte-macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.
4例对抗淋巴细胞球蛋白治疗无效的极重型再生障碍性贫血患者接受了重组人粒细胞巨噬细胞集落刺激因子（GM-CSF）治疗。1例有少量残留骨髓造血功能的患者，分别接受了2个疗程静脉注射GM-CSF（4微克/千克/天和8微克/千克/天）以及1个疗程皮下注射GM-CSF（4微克/千克/天），出现短暂反应。对传统治疗耐药的败血症和双侧肺炎得以缓解。3例无残留骨髓造血功能证据的患者对GM-CSF无反应。1例患者GM-CSF剂量增至32微克/千克/天，对造血功能无影响。GM-CSF剂量达16微克/千克/天时，即刻副作用轻微。然而，接受32微克/千克/天GM-CSF治疗的患者，GM-CSF可能与下腔静脉血栓形成的病理生理过程有关。我们得出结论，对于长期存在、严重且治疗抵抗的全骨髓造血功能衰竭的再生障碍性贫血，GM-CSF不能诱导造血。然而，对于有少量残留骨髓造血功能的患者，GM-CSF可能是治疗严重感染的一种有前景的辅助治疗方法。
